Triethylamine → 2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

HRID 1190521Notes

Reaction equation

HRID 1190521 reaction equation
OC(C(F)(F)F)=O.[NH:8]1[CH2:11][CH:10]([C:12]2[CH:33]=[CH:32][C:15]3[C:16]4[N:17]=[C:18]([C:24]5[N:25]([CH:29]([CH3:31])[CH3:30])[N:26]=[CH:27][N:28]=5)[S:19][C:20]=4[CH2:21][CH2:22][O:23][C:14]=3[CH:13]=2)[CH2:9]1.C(N(CC)CC)C.[CH:41]([S:43]([CH3:46])(=[O:45])=[O:44])=[CH2:42]>>[CH:29]([N:25]1[C:24]([C:18]2[S:19][C:20]3[CH2:21][CH2:22][O:23][C:14]4[CH:13]=[C:12]([CH:10]5[CH2:11][N:8]([CH2:42][CH2:41][S:43]([CH3:46])(=[O:45])=[O:44])[CH2:9]5)[CH:33]=[CH:32][C:15]=4[C:16]=3[N:17]=2)=[N:28][CH:27]=[N:26]1)([CH3:31])[CH3:30]

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 19354Methyl vinyl sulfoneHCID 866523168-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt

Product 1

HCID 582040292-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-[1-(2-methanesulfonyl-ethyl)-azetidin-3-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azuleneYield 68%

Procedure

To a solution of 8-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt 235 (200 mg, 0.42 mmol) in IMS (industrial methylated spirits, 3 mL) was added triethylamine (0.20 mL, 1.47 mmol) and methyl vinyl sulfone (0.09 mL, 1.05 mmol) and the reaction mixture was stirred at RT (room temperature) for 18 hours. The reaction mixture was concentrated in vacuo and the residue purified by flash chromatography (SiO2, 0-5% MeOH in DCM). Freeze-drying from methanol and water gave 320 as a pale yellow solid (135 mg, 68%). LCMS: RT=3.10 min, [M+H]+=474. 1H NMR δ (ppm) (DMSO-d6): 8.35 (1H, d, J=8.19 Hz), 8.11 (1H, s), 7.29 (1H, d, J=8.27 Hz), 7.20 (1H, s), 5.85-5.76 (1H, m), 4.41-4.35 (3H, m), 4.14 (3H, d, J=59.98 Hz), 3.68 (2H, s), 3.53-3.41 (3H, m), 3.13 (3H, s), 1.55 (6H, d, J=6.60 Hz). 2 Protons obscured by water peak

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue purified by flash chromatography (SiO2, 0-5% MeOH in DCM)
  3. dry with materialFreeze-drying from methanol and water

Sources & evidence

ORD record
ord-bd7c7038ed694bd4b2cb7e3002dd71e9
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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